Our lab is broadly interested in how bacteria adapt to stressful conditions. We primarily think about microbial stress through the lens of host-pathogen interactions, where microbial pathogens must survive within the chemically complex and dynamic host environment to cause disease. We are particularly interested in the capacity for the molecule nitric oxide (NO) to shape microbial survival, which is both a component of the host immune system but is also a crucial intermediate for microbial anaerobic respiration. What are the molecular and genetic determinants of microbial adaptation to NO, and how does the local environment shape these responses? Given the universality of NO in biology, we hope that our research at the host-pathogen interface will inspire investigations into the capacity of NO to tune diverse microbe-dominant ecosystems.
Investigating the biochemistry of secreted bacterial metabolites
One way that bacteria adapt to their environment is through the production of secreted metabolites, which are produced locally but can diffuse and have important implications on both the producer microbe and neighboring cells, whether those are other microbes or components of the host immune system. In addition to their known roles, secreted metabolites often have their own unique chemical properties that promote their environmental transformation into new compounds, especially when we consider that components of the environment like nitric oxide might react with these metabolites. To investigate these processes, we utilize (bio)chemical methods including chromatography and mass spectrometry approaches to answer the following questions: What is the chemical nature of transformed metabolites, and what are the consequences on the producing microbe as well as the community?
Biochemical assays
Small molecule extractions
Identifying genetic determinants of microbial stress response systems
The capacity of microbes to survive stressful conditions is often genetically-encoded. By using bacterial strains that are genetically tractable, we seek to understand which genes confer resistance to stressors in diverse contexts. We employ both targeted genetic tools to correlate genotypes with phenotypes, as well as high-throughput genetic screens to discover new genes involved in microbial stress response. How do these genetic circuits overlap or diverge to promote stress tolerance, and can we apply what we learn in one microbial species to understand stress responses in less genetically tractable organisms?
Bacterial stress resistance
Bacterial survival requires sensing and responding to the local environment. From the host-pathogen perspective, this means interfacing with the host immune system. Therefore, in addition to defining molecular mechanisms of stress tolerance in vitro, we also test the importance of these interactions in more complex ecosystems, including within biofilms, in competition with other microbes, or within the infection context using cell lines or murine infection models. These experiments are coupled with reporter systems and advanced imaging modalities to monitor microbial activity in situ. Specifically, do chemical transformations of microbial metabolites or genetic factors that promote survival impact biofilm formation or infection outcomes?
Note: animal work is not required.
Defining the contribution of bacterial metabolites and metabolisms to complex environments
Confocal microscopy of stratified bacterial biofilm
In vivo assessment of bacterial metabolism